Oleic Acid Could Act as a Channel Blocker in the Inhibition of nAChR: Insights from Molecular Dynamics Simulations

DIEGO OBIOL; MARÍA J. AMUNDARAIN; FERNANDO ZAMARREÑO; AGUSTÍN VIETRI; SILVIA ANTOLLINI; MARCELO D. COSTABEL

Journal of Physical Chemistry B

American Chemical Society

Año: 2024 vol. 128 p. 2398 - 2411

The activation of the muscular nicotinic acetylcholine receptor (nAChR) produces the opening of the channel, withthe consequent increase in the permeability of cations, triggering anexcitatory signal. Free fatty acids (FFA) are known to modulate theactivity of the receptor as noncompetitive antagonists, acting at themembrane−AChR interface. We present molecular dynamicssimulations of a model of nAChR in a desensitized closed stateembedded in a lipid bilayer in which distinct membranephospholipids were replaced by two different monounsaturatedFFA that differ in the position of a double bond. This allowed us todetect and describe that the cis-18:1ω-9 FFA were located at theinterface between the transmembrane segments of α2 and γ subunits diffused into the channel lumen with the consequent potentialability to block the channel to the passage of ions.